| 1. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 2. |
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| 3. |
- Farrell, William M., et al.
(författare)
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The dust, atmosphere, and plasma at the moon
- 2024
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Ingår i: Reviews in Mineralogy and Geochemistry, Mineralogical Society of America. - : Walter de Gruyter. - 1529-6466 .- 1943-2666. ; 89, s. 563-609
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 5. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 6. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 7. |
- Vorburger, Audrey, et al.
(författare)
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3D Monte-Carlo simulation of Ganymede's atmosphere
- 2024
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 409
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Tidskriftsartikel (refereegranskat)abstract
- We present new model results for H2O, O2, H2, O, and H in the atmosphere of Ganymede. The results are obtained from a collision-less 3D Monte-Carlo model that includes sublimation, ion and electron sputtering, and ion and electron radiolysis. Because Ganymede has its own magnetic field, its immediate plasma environment is particularly complex. The interaction between Ganymede's and Jupiter's magnetospheres makes it highly variable in both space and time. The recent Juno Ganymede flyby provided us with new data on the electron local environment. Based on the electron measurements recorded by the Jovian Auroral Distributions Experiment (JADE), we implement two electron populations, one for the moon's polar regions and one for the moon's auroral regions. Comparing the atmospheric contribution of these newly defined electron populations to the overall source and loss processes is one of the main goals of this work. Our analysis shows that for H2O, sublimation remains the most important source process even after accounting for the new electron populations, delivering more than three orders of magnitude more H2O molecules to the atmosphere than all other source processes combined. The source fluxes for O2 and H2, on the other hand, are dominated by radiolysis induced by the auroral electrons, assuming that the electron fluxes JADE measured during Juno's transit of Ganymede's magnetopause current layer are representative of auroral electrons. Atomic O and H are mainly added to the atmosphere through the dissociation of O2 and H2, which is primarily induced by auroral electrons. Our understanding of Ganymede's atmosphere today is mainly based on spectroscopic observations. The interpretation of spectroscopic data strongly depends on assumptions taken, though. Our analysis shows that for a holistic understanding of Ganymede's atmosphere, simultaneous observations of the moon's surface, atmosphere, and full plasma environment (thermal and energetic ions and electrons) at different times and locations (both with respect to Ganymede and with respect to Jupiter) are particularly important. Such measurements are planned by ESA's Jupiter ICy moons Explorer (JUICE), in particular by the Particle Environment Package (PEP), which will greatly advance our understanding of Ganymede and its atmosphere and plasma environment.
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| 8. |
- Fatemi, Shahab, et al.
(författare)
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Solar wind plasma interaction with Gerasimovich lunar magnetic anomaly
- 2015
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 120:6, s. 4719-4735
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first local hybrid simulations (particle ions and fluid electrons) for the solar wind plasma interaction with realistic lunar crustal fields. We use a three-dimensional hybrid model of plasma and an empirical model of the Gerasimovich magnetic anomaly based on Lunar Prospector observations. We examine the effects of low and high solar wind dynamic pressures on this interaction when the Gerasimovich magnetic anomaly is located at nearly 20 degrees solar zenith angle. We find that for low solar wind dynamic pressure, the crustal fields mostly deflect the solar wind plasma, form a plasma void at very close distances to the Moon (below 20km above the surface), and reflect nearly 5% of the solar wind in charged form. In contrast, during high solar wind dynamic pressure, the crustal fields are more compressed, the solar wind is less deflected, and the lunar surface is less shielded from impinging solar wind flux, but the solar wind ion reflection is more locally intensified (up to 25%) compared to low dynamic pressures. The difference is associated with an electrostatic potential that forms over the Gerasimovich magnetic anomaly as well as the effects of solar wind plasma on the crustal fields during low and high dynamic pressures. Finally, we show that an antimoonward Hall electric field is the dominant electric field for similar to 3km altitude and higher, and an ambipolar electric field has a noticeable contribution to the electric field at close distances (<3km) to the Moon.
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| 9. |
- Liuzzo, Lucas, et al.
(författare)
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On the formation of trapped electron radiation belts at Ganymede
- 2024
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 51:10
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Tidskriftsartikel (refereegranskat)abstract
- This study presents evidence of stably trapped electrons at Jupiter's moon Ganymede. We model energetic electron pitch angle distributions and compare them to observations from the Galileo Energetic Particle Detector to identify signatures of trapped particles during the G28 encounter. We trace electron trajectories to show that they enter Ganymede's mini-magnetospheric environment, become trapped, and drift around the moon for up to 30 min, in some cases stably orbiting the moon multiple times. Conservation of the first adiabatic invariant partially contributes to energy changes throughout the electrons' orbits, with additional acceleration driven by local electric fields, before they return to Jupiter's magnetosphere or impact the surface. These trapped particles manifest as an electron population with an enhanced flux compared to elsewhere within the mini-magnetosphere that are detectable by future spacecraft.
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| 10. |
- Liuzzo, Lucas, et al.
(författare)
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Variability in the Energetic Electron Bombardment of Ganymede
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:9
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Tidskriftsartikel (refereegranskat)abstract
- This study examines the bombardment of energetic magnetospheric electrons onto Ganymede as a function of Jovian magnetic latitude. We use the output from a three-dimensional, hybrid model to constrain features of the electromagnetic environment during the G1, G8, and G28 Galileo encounters when Ganymede was located far above, within, or far below Jupiter's magnetospheric current sheet, respectively. To quantify electron fluxes, we use a test-particle model and trace relativistic electrons at discrete energies between 4.5 keV =E = 100MeV while exposed to these fields. For each location with respect to Jupiter's current sheet, electrons of all energies bombard Ganymede's poles with average number and energy fluxes of 1 center dot 108 cm-2 s-1 and 3 . 109 keV cm-2 s-1, respectively. However, bombardment is locally inhomogeneous: poleward of the open-closed field line boundary, fluxes are enhanced in the trailing hemisphere but reduced in the leading hemisphere. When embedded within the Jovian current sheet, closed field lines of Ganymede's minimagnetosphere shield electrons below 40MeV from accessing the equator. Above these energies, equatorial fluxes are longitudinally inhomogeneous between the sub-Jovian and anti-Jovian hemispheres, but the averaged number flux (4 . 103 cm-2 s-1) is comparable to the flux deposited here by each of the dominant energetic ion species near Ganymede. When located outside of the Jovian current sheet, electrons below 100 keV enter Ganymede's minimagnetosphere via the downstream reconnection region and bombard the leading apex, while electrons of all energies are shielded from the trailing apex. Averaged over a full synodic rotation period of Jupiter, the energetic electron flux pattern agrees well with brightness features observed across Ganymede's polar and equatorial surface.
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